By Emily White
Following a long-time interest in biology and metabolic function, Charles Ikechukwu Opara works hard as a graduate student in the UW-Madison Genetics PhD Program and Alan Attie’s lab. His interest began back in high school, ignited by a curiosity in gene therapy. After receiving a BS degree from the University of Calabar in Nigeria, he worked for several years in the area of crop genetics, including work on a project focused on yam breeding funded by the Gates Foundation. These experiences motivated him for a PhD in Genetics.
“I was fascinated to learn that the most complex biological problems in organismal biology necessitated solutions to start at the molecular level,” he says.
Opara’s current research in the Attie lab is studying genetic variation in transcript isoforms, an area often overlooked in genetic mapping studies. He is on an upward climb in this research and was recently awarded a Stephen Babcock Graduate Research Fellowship from the Department of Biochemistry, along with a past OFP Scholarship from the Nigerian Education USA Programme. Opara provided some further insight into his research.
What are the big-picture questions of your research and what is more exciting/ innovative?
My research uses systems genetics to uncover the molecular mechanisms controlling transcriptomic regulation and metabolic outcomes. Genome-wide association studies have relied on gene-level estimates of mRNA expression as molecular traits, but recent work implicating alternative splicing mechanisms in disease suggests this approach limits
the discovery of novel genetic associations. To address this, I use the Diversity Outbred (DO) mouse stock, derived from eight inbred founder strains [outbred to produce] genetically unique and diverse animals. This population captures genetic diversity comparable to the entire human population (~40 million SNPs). Because key metabolic and regulatory pathways are conserved between mice and humans, quantitative trait loci identified in this population can be translated to human physiology.
We completed a large genetic screen of this mouse population (1,157 samples) split across two extreme diets and performed QTL mapping to identify loci associated with expression and splicing. Using allele-effect patterns, we found that genetic variation drives allele-specific isoform usage, producing isoforms whose genetic signals diverge from their aggregated gene- level effects: a genome-wide pattern attributable to post-transcriptional regulation. This argues for prioritizing isoform-level resolution in genetic association studies to maximize sensitivity and avoid signals missed by gene-level analyses alone.
Where is your research going next?
We just completed a manuscript describing this work. My current focus investigates how these mechanisms underlie alternative functions of these isoforms and how they influence metabolic outcomes. For these studies, I have available to me rich datasets consisting of metabolomics, lipidomics, and stable isotope tracer data from the same mouse cohort.
What is the single person, event, or experience that most influenced your trajectory to where you are today?
My thesis advisor, Alan Attie, has had the most influence on my trajectory so far. Working in the Attie lab has profoundly reshaped how I think about and approach scientific problems. I have come to appreciate several core values that make a good scientist, including taking an optimistic approach to even the hardest problems, driving collaborations, and never wanting to stop learning. He has been a wonderful teacher, and his mentorship has shaped not only the scientist I have become but the kind of mentor I hope to be.
What advice would you have for a young person interested in graduate school or research?
Love science. Be certain that you truly love it. A well-put-together application and good experiences will get you into grad school, but only true passion will see you through. It gets really challenging in grad school, and sometimes, you have to dig deep to find something to hold on to. For me, that has been my passion for scientific research. A lot of people underestimate how challenging it might get and end up quitting midway. I always advise getting some research experience before applying to grad school, and to pay attention not to how you feel when things work, but to how you feel during the long stretches between failed experiments, the troubleshooting, and the months when nothing works. Having a strong passion for science isn’t really about the thrill of a discovery, but the strength to keep pushing on the days when all seems hopeless. If you still want to be in the lab on those days, then you’re likely to succeed in grad school.
Opara has unique plans for his future education. “I love to cook and try out new recipes. I still hope to attend culinary school and try professional cooking someday.” He’s also cooking up plans to continue on to a Postdoc position with the intention of continuing his work on approaches that intersect quantitative genetics and metabolism.